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Rockefeller Student Sponsored Speaker 2018 Wiki
= Student Sponsored Speaker Candidates 2018 = Larry Abbott, Columbia University Computational and Mathematical Analysis of Neurons and Neural Networks Larry Abbott's research involves the computational modeling and mathematical analysis of neurons and neural networks. Analytic techniques and computer simulation are used to study how single neurons respond to their many synaptic inputs, how neurons interact to produce functioning neural circuits, and how large populations of neurons represent, store, and process information. Areas of particular interest include spike-timing dependent forms of synaptic plasticity, transformations of sensory encoding in olfaction, and the dynamics of internally generated activity and signal propagation in large neural networks. Most neural activity is generated internally but nervous systems are nevertheless highly sensitive to external influences such as sensory stimuli. We study how stimulus driven and internally generative activity interact and combine to produce responses. We also model how chaotic ongoing activity can be harnessed and controlled to produce useful motor output. We are interested in representing perception not as a passive analysis of sensory input, but as a dynamic process that involves modeling the external world, making inferences about predictable events and noting when something unexpected happens. This requires both representing sensory stimuli and modifying ongoing activity through synaptic plasticity. Lab Site https://en.wikipedia.org/wiki/Larry_Abbott H. Allen Orr, University of Rochester Dr. Orr is an evolutionary geneticist with several broad interests. Most of his research focuses on the genetics of speciation and the genetics of adaptation. In particular, he is interested in the genetic basis of hybrid sterility and inviability, e.g., how many genes cause reproductive isolation between species? What are the normal functions of these genes and what evolutionary forces drove their divergence? He studies these problems through genetic analysis of reproductive isolation between species of Drosophila. In his adaptation work, Dr. Orr is interested in theoretical rules or patterns that might characterize the population genetics of adaptation. He studies these patterns using both population genetic theory and experiment. Lab Site Wikipedia Michael Angelo, Stanford The Angelo Lab employs a method known as Multiplexed Ion Beam Imaging (MIBI) that uses secondary ion mass spectrometry to image antibodies tagged with isotopically pure elemental metal reporters. MIBI is capable of analyzing up to 100 targets simultaneously over a five-log dynamic range. Thus, MIBI enables highly multiplexed and sensitive immunohistochemistical analysis of complex tissues. Our lab applies MIBI to questions in the fields of cancer biology, infectious diseases, immune tolerance, allergy, and the maternal-fetal interface in addition to technology and methods development. Mike's academic background spans across the fields of physics, biochemistry, electrical engineering, and medicine. During his residency he became interested in developing novel methods for immunohistochemical multiplexing using mass spectrometry leading to the development of MIBI during his postdoctoral work in the Nolan lab at Stanford University. Mike is now interested in optimizing MIBI and other mass reporter-based technologies further with the goal of identifying new transcriptional and translational signatures in solid tissue malignancies, and in allergic and other immunological disorders, that can be used to improve clinical diagnosis and treatment Lab Site Brigitte Baptiste, Humboldt Institute, Colombia Brigitte Baptiste has had a long career in both nonprofit and academic spheres. As a student in 1982, she co-founded the environmental nonprofit Corporación Grupo Ecológico GEA, which she would later serve as director from 1984 to 1991. From 1991 to 1996, she served as a professor in the Institute of Environmental Studies and Development (IDEADE) at Pontifical University, during which she edited Ambiente y Desarrollo (IDEADE-PUJ). After 1996, she coordinated the Program for Biodiversity Use and Valuation at the Humboldt Institute and consulted for numerous nonprofits, including WWF Colombia. She returned to Pontifical University from 2002 to 2009 to teach and research as an assistant professor.3 She has been the director of the Humboldt Institute since 2011 As director, Baptiste represents Colombia's scientific authority to the Convention on Biological Diversity (CITES) (International Convention on Wildlife Trade) and SBSTTA (Subsidiary Body of Scientific, Technical and Technological Advice). She serves on the Intergovernmental Panel on Biodiversity and Ecosystem Services (IPBES) as a member of its Global Panel of 25 experts (MEP) on behalf of Latin America and the Caribbean (2015-2017). There, she co-chairs working groups on Indigenous and Local Knowledge, as well as on Policy Tools and Methodologies. She is also a member of the IAI's Science Policy Advisory Committee (Inter-American Environmental Initiative for Global Change) and the scientific committee of the global program PECS (Ecosystem Change and Society).1 She was a prominent voice advocating for a peace deal in the Colombian Civil War.5 Wikipedia Staci Bilbo, Harvard The Bilbo Lab focuses on the study of neuroimmune interactions in brain development, using pre-clinical models. We collaborate with clinical research groups to translate our findings to human populations. We are particularly interested in the role of immune molecules in both normal and disrupted brain development, based on evidence from human and animal studies that immune system dysfunction or inflammation may be critical in a number of neurodevelopmental disorders, including schizophrenia, cognitive and mood disorders, and autism. A particular focus is on the resident immune cells of the brain, microglia, including their development and function in response to early life inflammatory signals. The overarching goal of research in the Bilbo lab is to understand the mechanisms by which the immune, endocrine, and nervous systems interact, and how these interactions influence behavioral outcomes such as cognition, emotion and addiction. The immune system is well characterized for its critical role in host defense. Far beyond this limited role however, there is mounting evidence for the vital role the immune system plays within the brain, in both normal, “homeostatic” processes (e.g., sleep, metabolism, memory), as well as in pathology, when the dysregulation of immune molecules may occur. We believe this recognition is especially critical in the area of brain development. Microglia and astrocytes, the primary immunocompetent cells of the CNS, are involved in every major aspect of brain development and function, including axonal migration and synaptogenesis, synaptic pruning, apoptosis, and angiogenesis. Cytokines such as interleukin-IL-1 beta, tumor necrosis factor TNF, and IL-6 are produced by glia within the CNS, and are implicated in synaptic scaling, long-term potentiation, and neurogenesis. Importantly, cytokines are involved in both injury and repair, and the conditions underlying these distinct outcomes are under intense investigation and debate. Notably, evidence from both animal and human studies implicates the immune system in a number of disorders with known or suspected developmental origins, including schizophrenia, autism, and cognitive dysfunction. Twitter Lab Site Jesse Bloom, Fred Hutchinson Cancer Center Rapid evolution is a defining feature of many of the most medically problematic viral diseases, including influenza. Although this rapid evolution is usually bad from the perspective of public health, it offers a unique vantage from which to study a range of important questions in biology. For instance, consider the figure to the left, which summarizes the evolution of the human and swine descendants of the 1918 influenza pandemic. It took less than 90 years for these two viral lineages to become as different at the protein level as humans and pigs themselves – and the full sequences of many of the evolutionary intermediates are known. Furthermore, this is just one example of the many viral evolutionary histories that can be reconstructed in remarkable detail. We apply a combination of experimental and computational approaches to use the information in such histories to address questions such as: What are the constraints that shape evolutionary trajectories? Can we use an understanding of these constraints to better predict future viral evolution? Can we identify the underlying molecular changes that enable phenotypically obvious and medically important evolutionary events such as drug resistance, immune escape, and host-species transfer? When a single ancestor gives rise to multiple parallel lines of descent (such as the human and swine lineages in the figure below), in what ways are the subsequent molecular changes similar, and how do they differ? Can we identify selection pressures (such as variation in the host immune systems) responsible for the differences? Why do some viruses (such as influenza) so readily escape pre-existing immunity, while others with similarly high mutation rates (such as polio) can easily be tamed by a vaccine? Can we identify physical properties that contribute to differences in molecular evolvability? How can we create therapeutics and vaccines that are more resistant to viral evolutionary escape? Lab Site HHMI Anne Churchland, Cold Spring Harbor Labs Understanding how brains makes decisions is critical for gaining insight into complex cognition. When making decisions, humans and animals can flexibly integrate multiple sources of information before committing to action. The ability to flexibly use incoming information distinguishes decisions from reflexes, offering a tractable entry point into more complex cognitive processes defined by flexibility, such as abstract thinking, reasoning and problem solving. In my laboratory, we investigate the neural circuits underlying decision-making. We measure and manipulate neurons in cortical and subcortical areas while animals make decisions about sensory signals. To connect the neural responses with behavior, we use mathematical analyses aimed at understanding what information is represented at the level of neural populations, both at a given moment and over time. Understanding neural population activity will bolster our long term goal: to determine how the brain can make decisions that integrate inputs from our multiple senses, stored memories and innate impulses. Lab Site Wikipedia Rui Costa, Columbia Throughout our life we learn to perform a variety of different actions to impact the world around us, and to obtain the outcomes we want. Many of these actions are learned by associating specific stimuli to particular responses, thereby building sensorimotor repertoires, where the occurrence of the stimulus leads to the execution of the action. But many other actions are self-paced, and learned/shaped based on their consequences. Such actions are initiated and performed in a spontaneous manner, and if some desirable outcome (a reward, a stimulus, even another action) occurs as a consequence, we learn to do them again, and to shape their execution to achieve that goal. This process of learning from consequence could be viewed conceptually as a motorsensory process, which is impaired in conditions affecting self-paced action generation, such as Parkinson’s disease, and action control, such obsessive-compulsive disorder. The efforts of our laboratory have been dedicated to understanding the circuits and the mechanisms underlying the generation of novel self-paced actions, and the shaping of these actions into complex action repertoires based on the consequences of their execution. Understanding this process, through trial and feedback, requires mechanistic insight into how self-paced actions are initiated, how they can be selected/initiated again, how feedback can shape their execution and organization, and what drives the actions to be performed in a particular situation. Lab Site Lab Site 2 Michael Dickinson, Caltech The Dickinson Lab is broadly interested in the neural and biomechanical basis of behavior. We employ the fruit fly, Drosophila melanogaster as a model system, because it exhibits a rich diversity of innate and learned behaviors and may be studied using state-of-the art genetic approaches. We attempt to leverage these genetic tools by engineering custom instruments that enable the study of behavior from the cellular to ecological level. We are dedicate do interdisciplinary approaches, and the students and post-docs in the lab originate from diverse disciplines including physics, engineering, computer science, and biology. The lab focuses primarily, but not exclusively, on flight behavior. Active flight, which has only evolved four times in the history of life, is a specialized form of locomotion that pushes the envelope of organisms design. Flies, for example, possess the fastest known visual systems, among the most powerful and fast contracting muscles, and a remarkable set of sensory organs including tiny gyroscopes called halteres. Fruit flies are able to travel for over 3 million body lengths per day in search of feeding sites and mates, and can execute evasive banked turns from attacking predators within a fraction of a human eye blink. These and other behaviors motivate both discovery- and hypothesis-driven research projects. Lab Site Wikipedia Laurent Keller, University of Lausanne The goal of our group is understand the principles governing the evolution of animal societies and the ecological and evolutionary consequences of social life. To study these questions we combine disciplines of animal behaviour, ecology, evolutionary genetics and genomics. Our current interests include: Ageing in social insects, Genetic, ecological and molecular bases for variation in social systems, Division of labour in insect societies, Causes and consequences of genetic caste determination, Biological invasions, Expermental robotics. Wikipedia Bill Hansson, Max Planck Institute for Chemical Ecology We study odor-directed behavior and its underlying neurobiological substrate in arthropods from a functional and evolutionary perspective. In drosophilid flies our main objective is to understand the evolution of olfactory functions in an ecological context. By studying closely related species living under different ecological conditions it is possible to understand how habitat and food-choice have affected the evolution of the sense of smell. We are also investigating the direct function of the Drosophila melanogaster olfactory system by looking at transduction mechanisms, and coding and connectivity at different neural levels, as well as the behavioral outcome of olfactory processing. In sphingid moths we want to understand how different host plant associations have affected olfactory function and behavior. Both oviposition site search and nectar feeding are heavily dependent on odor information. To understand the origin of the specific traits characterizing insect olfaction we study the most basal insects like bristletails and firebrats. In all these systems the complete neuroethological chain of events is studied, from single molecules and genes, to neurons, to whole organism responses. To perform this research we make use of modern neurobiological techniques as optical imaging, patch clamping, extra- and intracellular recording, and two photon confocal microscopy. We also use molecular techniques and bioinformatics. Behavioral responses are studied in the field, in wind tunnels and in laboratory bioassays. Wikipedia Wolf-Dietrich Heyer, UC Davis Mechanism of homologous recombination in eukaryotes DNA double-stranded breaks (DSB) are recognized as the major genotoxic lesion of ionizing radiation. The use of ionizing radiation in medical diagnostics and therapy mandates an exact understanding of the biological processes surrounding the formation of radiation damage, its recognition, its repair, and of other cellular responses (e.g. apoptosis) to DSBs. Moreover, a class of microbial secondary metabolites utilized as anti-cancer drugs (e.g. bleomycin) also causes DSBs. To potentially enhance the efficacy of treatment and to minimize side-effects it is crucial to understand the full range of cellular responses to this type of DNA damage. Thus, understanding the cellular responses to ionizing radiation constitutes a major goal in biomedical research. The laboratory of Dr. Heyer is internationally recognized for its expertise in protein biochemistry with significant contributions to establish new paradigms and elucidate the fundamental mechanisms of homologous recombination and recombinational DNA repair. The most significant contribution range from the original discovery of Mus81 (Interthal et al. 2000), the definition of its substrate range (Ehmsen & Heyer, 2008, 2009) and of its cleavage mechanism (Mukherjee et al. 2014), to the identification of direct regulation of DNA repair by the DNA damage checkpoints and nonsense-mediated decay (Bashkirov et al. 2000, Herzberg et al. 2006, Janke et al. 2016), the role of Rad54 and Sgs1-Top3-Rmi1 in D-loop formation and disruption, respectively (Wright & Heyer, 2014, Fasching et al. 2015) and to turnover Rad51 from dsDNA (Solinger et al. 2002, Li et al. 2009), the first reported (concomitant with two other laboratories) purification of full-length human BRCA2 (Liu et al. 2010), the demonstration of the role DNA Polymerase delta and lambda in HR (Li et al. 2009; Sneeden et al. 2013, Meyer et al. 2015), and the discovery of a novel anti-anti-recombination mechanism (Liu et al. 2011). Lab Site Scott Waddell, University of Oxford Directed behaviour emerges from neural integration of sensory stimuli, memory of prior experience and internal states. The Waddell group seeks an understanding of these conserved neural mechanisms using genetically-encoded tools and the relatively small brain of Drosophila. By temporally controlling neural function memories can be implanted and internal states altered so that most flies behave according to our direction. Such recent studies have revealed a role for distinct subsets of dopaminergic neurons that innervate the mushroom bodies in reward learning, the control of motivated behaviour and the re-evaluation of learned information. The unique cellular resolution of the reinforcement system of the fly permits a detailed investigation of how it really works. One might interpret the relative ease of altering behaviour to indicate that everything is simple in the fly brain. However, complexity arises in unexpected ways. Some transposable elements are expressed in long-term memory relevant neurons of the mushroom body. We are interested in how transposons might contribute to gene expression, cellular and organismal individuality. Lab Site Wikipedia https://www.dpag.ox.ac.uk/research/waddell-group Jonathan Weissman, UCSF Our laboratory is looking at how cells ensure that proteins fold into their correct shape, as well as the role of protein misfolding in disease and normal physiology. We are also developing experimental and analytical approaches for exploring the organizational principles of biological systems and globally monitoring protein translation through ribosome profiling. To ensure proper folding, cells have evolved a sophisticated and essential machinery of proteins called molecular chaperones that assist the folding of newly made polypeptides. The importance of proper protein folding is underscored by the fact that a number of diseases, including Alzheimer's and those involving infectious proteins (prions), result from protein-misfolding events. My research focuses on identifying and understanding the machinery necessary for efficient folding, as well as studying the mechanism and consequences of protein misfolding. We are also developing experimental and analytical approaches for exploring the organizational principles of complex biological systems and for monitoring protein translation in vivo with unprecedented precision and depth. The ability to bridge large-scale approaches and mechanistic investigations is a key focus of my lab. Beyond the immediate payoff of these efforts, I hope our work will contribute to the broader goal of developing more principled, less ad hoc approaches for defining gene functions. Wikipedia HHMI Mark Schnitzer, Stanford The long-term goal of our research is to advance experimental paradigms for understanding normal cognitive and disease processes at the level of neural circuits, with emphasis on learning and memory processes. By contrast, much current research on learning and memory concentrates on levels of organization in the nervous system that are either more macroscopic (e.g. in cognitive psychology) or more microscopic (e.g. in synaptic physiology). Our approach combines behavioral, electrophysiological, and computational methodologies with high-resolution fluorescence optical imaging that is capable of resolving individual neurons and dendrites. By necessity, we aim to advance imaging methods so that we can examine dynamics of neuronal populations or of dendritic compartments in behaving animals. En route, we are also performing experiments on circuit properties in anesthetized animals, such as the studies that use our newly invented fluorescence endoscopes for examining hippocampal cells and dendrites in vivo. We seek explanations that span different levels of organization, from cells to entire circuits. We work with both genetic model organisms, mice and fruit flies, and human subjects. Our research emphasizes understanding the control and learning of motor behaviors, as well as the potential application of our newly developed imaging techniques to clinical use in humans. https://pyramidal.stanford.edu/ https://www.hhmi.org/scientists/mark-j-schnitzer Akiko Iwasaki, Yale Innate immunity; Autophagy; Inflammasomes; sexually transmitted infections; Herpes simplex virus; human papillomavirus;respiratory virus infections; Influenza infection; T cell immunity; Commensal bacteria Research Summary The mucosal surfaces represent major sites of entry for numerous infectious agents. Consequently, the vast mucosal surfaces are intricately lined with cells and lymphoid organs specialized in providing protective antibody and cellular immunity. One of the most fundamental issues in this field concerns how antigens in the mucosa are taken up, processed, and presented by antigen presenting cells. Our laboratory's goal is to understand how immunity is initiated and maintained at the mucosal surfaces, particularly by the dendritic cells (DCs), through natural portals of entry for pathogens that are of significant health concerns in the world. We focus on understanding how viruses are recognized (innate immunity) and how that information is used to generate protective adaptive immunity. We study immune responses to herpes simplex viruses in the genital tract and influenza infection in the lung. Our recent focus also includes the study of how autophagy mediates innate and adaptive immune responses to these and other viral pathogens. Our ultimate goal is to utilize the knowledge we gain through these areas of research in the rational design of effective vaccines or microbicides for the prevention of transmission of viral and bacterial pathogens. wikipedia Lab Site Mike Laub, MIT Toxin-antitoxin systems, Cell cycle regulation, Chromosome structure and organization. Our lab studies the molecular mechanisms and evolution of information processing at the cellular level. A defining and essential characteristic of cells is an ability to regulate their own behavior, modulating gene expression, cellular structures, motility, or metabolic state to ensure survival and proliferation. This regulatory capacity stems in large part from the coordinated action of signal transduction pathways that process information from the environment or internal cellular state. Using bacteria as model organisms, my lab aims to (i) elucidate the detailed molecular mechanisms responsible for the remarkable information-processing capability of cells, and (ii) understand the selective pressures and mechanisms that drive the evolution of signaling pathways. Our work is rooted in a desire to develop a deeper, fundamental understanding of how cells function and evolve, but it also has important medical implications, as many signaling pathways in pathogenic bacteria are needed for virulence. Specific projects in our lab fall into four general areas: (1) We examine the mechanisms through which bacterial cells evolve new signaling pathways. These studies include experimental investigations of protein evolution both in vitro and in vivo, ancestral protein reconstruction, directed evolution studies, and the design of synthetic signaling circuits. We focus in particular on two-component signaling systems. (2) We investigate toxin-antitoxin systems in bacteria, exploring their induction, mechanisms of action, specificity, and evolution. (3) We study the regulatory circuits that control cell cycle progression and cellular asymmetry in Caulobacter crescentus. We use genetics, biochemistry, and computational methods along with new fluorescence microscopy and deep-sequencing methods to dissect cell cycle control. (4) We are probing the origins and consequences of chromosome structure and organization in bacteria, using microscopy, Hi-C, genetics, and computational/evolutionary analyses. Lab Site David Liu, Harvard Professor Liu's research integrates chemistry and evolution to illuminate and program biology. His group's major research interests include (i) the discovery of therapeutically relevant synthetic molecules using DNA-templated organic synthesis, a technique developed in his laboratory, and Darwinian selection; (ii) the characterization and engineering of genome-editing proteins towards next-generation human therapeutics; and (iii) the laboratory evolution and delivery in vivo of proteins that modify information flow in human cells Next-Generation Macromolecular and Small-Molecule Tools for the Understanding and Treatment of Disease The vast majority of current therapeutic agents function by binding to disease-associated macromolecules and modulating their activity. Recent developments, however, have made increasingly realistic the possibility of developing next-generation therapeutics that do not simply bind targets, but instead alter the covalent structure of genes and gene products in ways that can more effectively treat—or even cure—many diseases. While the possibility of precisely manipulating genes and proteins in mammalian cells and, eventually, in humans, has enormous potential, several major challenges must be overcome to fully realize this vision. Perhaps the most significant of these challenges are (i'') the efficient creation of the macromolecules that are needed to alter genomes or proteomes with a high degree of selectivity and potency, and (''ii) the efficient delivery of macromolecules into target cells at therapeutically relevant doses in vitro and, especially, in vivo. To realize a vision in which arbitrary genes or proteins can be manipulated in mammalian cells to treat disease will require novel approaches to rapidly generating macromolecules with precise, tailor-made properties, and to delivering therapeutic macromolecules into cells. These approaches will interface in powerful ways with recently discovered genome-editing proteins, such as CRISPR/Cas9 and TALE repeat arrays, that enable the targeted manipulation of disease-associated genes in live animals. New technologies, such as phage-assisted continuous evolution (PACE), can rapidly evolve these proteins toward variants with increased therapeutic relevance and enhanced abilities to illuminate disease biology. In addition, laboratory-evolved forms of other macromolecules, including proteases, recombinases, and sortases, that selectively manipulate the covalent structure of specific genes and proteins, will also play key roles in enabling next-generation therapeutics. Complementing the development of macromolecular tools and therapeutics, the development of small molecules that can modulate the biological activities of targets implicated in human diseases, especially those without an underlying genetic basis, will continue to be an essential activity that connects new biological insights with leads for therapeutic development. Some targets may only be addressable using macromolecules by virtue of their binding energies and ability to catalyze transformations such as manipulating the covalent structure of genes and proteins. For other targets, however, small molecules will likely remain the most accessible class of agents to modulate activities in therapeutically relevant contexts. Therefore, the development and application of new, highly efficient small-molecule discovery technologies, such as the synthesis and selection of DNA-encoded small-molecule libraries against many disease-associated targets in a single experiment, will be crucial.. Lab Site Wikipedia Gilles Laurent, MPI Brain, Frankfurt Computation in three-layered cerebral cortex ''' '''Our laboratory is interested in the behavior, dynamics and emergent properties of neural systems (typically, networks of interacting neurons or neuron populations), especially as these properties relate to neural coding and sensory representation. The lab focuses principally on olfactory and visual areas, combining experiments, quantitative analysis and modeling techniques. We tend to use "simpler" experimental systems such as the brains of insects, fish and reptiles to facilitate the identification, mechanistic characterization and computational description of functional principles. Since moving to the Max Planck Institute for Brain Research in Frankfurt, the lab's experimental focus has moved to reptilian cortex, with an emphasis on olfactory and visual areas. The choice of this experimental system is guided by several reasons: (1) Simplicity: Reptilian cerebral cortex has a relatively simple architecture, at least when compared to that of mammalian isocortex: reptilian cortex contains only three layers, of which only two (LI and LIII) are neuropilar and mainly synaptic; in this it is similar to mammalian hippocampus and to olfactory cortex (archi-/paleocortices). As in piriform cortex and hippocampus also, only layer II is enriched in cell bodies, containing the somata of spiny pyramidal cells. Finally, reptilian cortex also appears to be relatively homogeneous across sensory areas. (2) Evolution: Turtles are among the closest links to the stem amniote ancestors of today's mammals, reptiles (and birds). While it is most likely that today's turtles evolved from, and are thus not identical to their ancient ancestors, it remains that understanding the computational architecture of their cortex could help reveal the ancestral design of mammalian olfactory cortex and hippocampal formation and more generally, reveal the functional logic of the earliest modules or computational building blocks of cerebral cortex in vertebrate evolution. (3) Experimental: Turtles are aquatic animals; they have evolved diverse metabolic mechanisms for resistance to anoxia, making brain tissue particularly suitable to in vitro experimentation. (4) Behavior: Finally, despite a reputation for indolence if not somnolence (turtles are, like all reptiles, poikilotherms and tend to enjoy sitting in the sun), many turtle species are predatory, active and highly visual as well as olfactory. They can be trained in a variety of experimental paradigms. They thus offer an excellent behavioral repertoire for combination with Lab Site Robert Malenka, Stanford Long-lasting activity-dependent changes in the efficacy of synaptic transmission play an important role in the development of neural circuits and may mediate many forms of learning and memory. Work from my laboratory over the last 10 years has demonstrated that there are a variety of related but mechanistically distinct forms of synaptic plasticity. A major goal of my laboratory is to elucidate both the specific molecular events that are responsible for the triggering of these various forms of synaptic plasticity and the exact modifications in synaptic proteins that are responsible for the observed, long-lasting changes in synaptic efficacy. To accomplish this we use cellular electrophysiological recording techniques to examine synaptic plasticity in a variety of different in vitro preparations including thin slices of various regions of the rodent brain and primary neurons in culture. We also use cell biological and molecular techniques to examine the activity-dependent modulation of neurotransmitter receptors and to express dominant negative forms of various synaptic proteins so that their exact functions can be determined. An additional complementary approach has involved examining synaptic physiology and synaptic plasticity in various mutant mouse lines lacking specific synaptic proteins. A related but independent area of research in my laboratory is the elucidation of the synaptic action of drugs of abuse such as the psychostimulants cocaine and amphetamine. Toward this end, we have developed in vitro slice preparations of the nucleus accumbens and ventral tegmental area, brain regions which are thought to mediate several of the behavioral effects of drugs of abuse. We have characterized a novel form of synaptic plasticity in the nucleus accumbens and have done an extensive pharmacological characterization of the synaptic effects of dopamine, cocaine, and amphetamine. Currently we are examining in more detail the underlying mechanisms of dopamine's actions and determining how chronic treatment with drugs of abuse affect the synaptic responses of nucleus accumbens and ventral tegmental area cells. Because chronic exposure to drugs of abuse elicit long-term adaptive changes in critical neural circuits, it is hoped that the knowledge gained from the work on the molecular mechanisms underlying synaptic plasticity will provide important clues to the molecular mechanisms underlying the development of tolerance, dependence and addiction. Lab Site Wikipedia Harmit Malik, Fred Hutch Evolutionary Arms Races Our genomes are a tenuous conglomerate of different genetic entities, each trying to maximize their own evolutionary success, often at great cost to their genomic neighbors. As expected, this conflict can create problems for the host organism. My lab is interested in evolutionary studies of genetic conflict to gain insight into their mechanisms and consequences. We study genetic conflicts primarily in three systems: Drosophila, primates and yeast. While there are a number of investigative projects that are going on at any given time in the lab, our focus is on three conflicts in particular: * Centromeres * Innate and intrinsic immunity against viruses in primates * Mobile genetic elements in Drosophila More information about each of these projects and the rationale behind them can be found on our Projects page Lab Site Garry Nolan Mass Cytometry, Multiplexed Ion Beam Imaging (MIBI), phospho flow. We use multiparametric single-cell analysis to study hematopoiesis, cancer and leukemia, autoimmunity and inflammation. We also develop computational approaches for network and systems immunology. Our most recent efforts are focused on a single cell analysis advance using a mass spectrometry-flow cytometry hybrid device, the so-called “CyTOF”. The approach uses an advanced ion plasma source to determine the levels of tagged reagents bound to cells—enabling a vast increase in the number of parameters that can be measured per cell. Our laboratory has already begun a large scale mapping of the hematopoietic hierarchy in healthy human bone marrow at an unprecedented level of detail. We are working to enable a deeper understanding not only of normal immune function, but also detailed substructures of leukemias and solid cancers as well as autoimmunity and pathogen effects upon the immune system. Lab Site Bernardo Sabatini In the first few years of life, humans tremendously expand their behavioral repertoire and gain the ability to engage in complex, learned, and reward-driven actions. Similarly, within a few weeks after birth mice can perform sophisticated spatial navigation, forage independently for food, and engage in reward reinforcement learning. Our laboratory seeks to uncover the mechanisms of synapse and circuit plasticity that permit new behaviors to be learned and refined. We are interested in the developmental changes that occur after birth that make learning possible as well as in the circuit changes that are triggered by the process of learning. Lastly, we examine how perturbations of these processes contribute to human neuropsychiatric disorders such as Tuberous Sclerosis Complex and Parkinson’s Disease. The laboratory examines the structure and function of synapses and the relationship between synapse function and animal behavior. This includes integrative studies of how synaptically connected networks of neurons (i.e. circuits) develop and function as well as biophysical studies of how an individual synapse operates. We are particularly interested in how the intrinsic properties of synapses, the action of neuromodulatory molecules, and the topography of the neural network interact to determine the function, and dysfunction, of a circuit. Wikipedia Lab Site Wikipedia Category:Browse